Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The duration of action and potency of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidases 24.11 and 24.15. Whereas endopeptidase 24.11 cleaves enkephalin pentapeptides, endopeptidase 24.15 degrades longer-chained opioids including dynorphin A1-8 and met-enkephalin-Arg6-Gly7-Leu8 (MERGL). Inhibitors of endopeptidase 24.11 and 24.15 both increase basal nociceptive thresholds and respective forms of opioid antinociception. Acute exposure to certain environmental stressors can produce antinociception which is opioid mediated; inhibitors of endopeptidase 24.11 potentiate this effect. The present study evaluated whether central administration of a selective inhibitor of endopeptidase 24.15, N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) increased antinociception following intermittent cold-water swims (ICWS) in rats. cFP-AAF-pAB (0.25-25 nmol, ICV) dose-dependently increased ICWS antinociception on the tail-flick and jump tests without affecting basal nociceptive thresholds. The opioid mediation of ICWS antinociception was confirmed by significant reductions in this response following naloxone. These data indicate that longer-chained endogenous opioid peptides participate in the antinociception induced by ICWS.
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PMID:Increases in opioid-mediated swim antinociception following endopeptidase 24.15 inhibition. 166 30

Intermediate pituitaries of the reptile, Anolis carolinensis, were separately pulse labeled with [3H]Trp and [3H]Tyr. The major form of alpha-MSH was purified by immunoprecipitation and isolated by reverse phase HPLC. Tryptic peptide analysis indicated that the [3H]Trp-labeled C-terminal fragment of Anolis alpha-MSH had the same retention time as mammalian ACTH(9-13) amide; however, the [3H]Tyr-labeled N-terminal fragment did not coelute with either mammalian ACTH(1-8) or N-acetyl-ACTH(1-8). Purification of alpha-MSH from 76 Anolis intermediate pituitaries confirmed that a sequence change had occurred in the N-terminal region of Anolis alpha-MSH. The tissues were acid extracted and purified by Sephadex G-25 chromatography and reverse phase HPLC to yield 4.5 micrograms of purified Anolis alpha-MSH for amino acid composition analysis and automated Edman degradation sequence analysis. The major form of Anolis alpha-MSH is nonacetylated and has the following novel primary sequence: Ser-Tyr-Ala-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro(Val-amide). The presence of Val-amide was verified by immunological analysis, tryptic peptide analysis and amino acid composition analysis.
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PMID:Detection of a novel sequence change in the major form of alpha-MSH isolated from the intermediate pituitary of the reptile, Anolis carolinensis. 166 89

In the presence of physiological cations (in Krebs-4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid buffer) at 37 degrees C the Ki value's of beta-endorphin for mu- and delta-opioid receptor binding sites in rat neocortical membranes, labeled with [3H][D-Ala2,MePhe4,Gly- ol5]enkephalin (DAMGO) and [3H][D-Ala2-D-Leu5]enkephalin (in the presence of unlabeled DAMGO), respectively, amounted to about 9 and 22 nM. Surprisingly, a very different selectivity pattern for the endogenous opioid peptide was found when the affinity of beta-endorphin for functional presynaptic opioid receptors was examined. Thus, beta-endorphin strongly inhibited the electrically evoked release of [3H]NE from rat neocortical slices with an IC50 value of about 0.5 nM, whereas [14C] acetylcholine release from neostriatal slices was inhibited with an IC50 value of about 100 nM. On the other hand, the electrically evoked release of [3H]dopamine from striatal slices was not affected by beta-endorphin. The inhibitory effects of DAMGO and beta-endorphin on [3H]NE release from neocortical slices were equally well antagonized by naloxone. Moreover, 10 nM of the highly selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen- Thr-NH2 antagonized competitively the inhibitory effect of beta-endorphin on [3H]NE release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-endorphin: a highly selective endogenous opioid agonist for presynaptic mu opioid receptors. 167 39

Four experiments were done to determine which receptor type(s) mediates the effects of third ventricular microinjections of four opioid peptide agonists on blood levels of glucose, free fatty acids, and corticosterone. Tests were performed in unanesthetized adult male albino rats having chronic intraventricular cannulas; blood samples were taken from the tail tip at 0, 15, 30, 60, 90, and 120 min postmicroinjection. In experiment 1, the agonists DAGO (Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol), beta-endorphin, DSLET (d-Ser2-Leu-enkephalin-Thr), and dynorphin A-(1-17) (0, 0.3, 1, 3, and 10 nmol/rat) produced three distinct patterns of changes in serum glucose, free fatty acid, and corticosterone values. Experiment 2 showed that the effects of DAGO and beta-endorphin were inhibited by prior injection with the opiate-receptor blocker naloxone (1 mg/kg sc) and that the effects of dynorphin were not diminished. Experiment 3 determined that dynorphin effects were also not diminished by naloxone given intraventricularly. Experiment 4 found that blockade of the mu-receptor by intraventricular pretreatment with the specific antagonist beta-funaltrexamine (20 micrograms/rat, 24 h before) completely abolished the effects of DAGO and beta-endorphin on glucose and corticosterone. The mu-receptor is critical to the mediation of the hyperglycemia and hypercorticosteronemia induced by the central administration of opiate agonists. These results imply that mu-opioid binding sites previously identified in central autonomic regions may be involved in the regulation of circulating glucose and corticosterone.
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PMID:mu-receptor mediates elevated glucose and corticosterone after third ventricle injection of opioid peptides. 167 42

Four fatty acid conjugates of a cyclic lactam-bridged alpha-MSH fragment analogue were synthesized and their potencies and biological activities compared in several melanotropin bioassays. Palmitoyl, myristoyl, decanoyl, and hexanoyl conjugates of H-Asp-His-D-Phe-Arg-Trp-Lys-NH2 were prepared. In the in vitro mouse melanoma cell assay, each of the conjugates was 10-100 times more potent than alpha-MSH or the substrate peptide in elevating tyrosinase activity. The shorter conjugates of hexanoic and decanoic acid were as potent as alpha-MSH in the lizard skin bioassay, whereas the longer myristoyl and palmitoyl analogues were about 100 times less potent. The potency of the myristoyl and palmitoyl conjugates increased with time in contact with the skins. These observations may be related to the more lipid-like nature of these peptide-fatty acid conjugates. Each of the conjugates exhibited prolonged melanotropic activity in the lizard skin bioassays and in the mouse S91 melanoma tyrosinase bioassay, since the biological response continued following removal of the conjugates from the incubation media. The prolonged residual melanotropic activity resulted from conjugation of the fatty acids to the MSH fragment analogue since the analogue itself did not exhibit prolonged activity.
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PMID:Synthesis and biological activities of fatty acid conjugates of a cyclic lactam alpha-melanotropin. 173 18

The substrate specificity of polysome rat liver N alpha-acetyltransferase (NAT) has been examined by utilizing a series of synthetic and natural substrates that has been systematically altered with respect to N-terminal sequence and length. Families of peptides of the structure S-Y-S-G-G-L-L-L were generated by successively replacing the N-terminal serine, the penultimate tyrosine, and the antepenultimate serine with all 19 commonly occurring amino acids, which were then assessed for their reactivity with the rat liver enzyme. Only peptides with N-terminal serine, alanine, methionine, leucine, and phenylalanine were modified. Glycine, lysine, arginine, valine, isoleucine, and tryptophan in the second position are (with N-terminal serine) strongly inhibitory, and proline completely blocks modification. Third-position substitutions have less of an effect on NAT activity with glycine, aspartic acid, glutamic acid, and tryptophan being most inhibiting (with N-terminal Ser-Tyr). These observations are generally in agreement with in situ modifications although there are some significant differences particularly with respect to the amino-terminal residues. Optimal chain length was determined to be 10-11 residues with either synthetic peptides of the structure S-Y-S-(G)n-L-L-L or adrenocorticotropin (ACTH) sequences ranging from 8 to 39 residues. The ACTH peptides were generally found to be severalfold better substrates than the corresponding synthetic ones. Activity was not affected by increased chain length beyond approximately 17 residues. These data support the view that polysome-catalyzed N alpha-acetylation occurs as a cotranslational event on nascent chains of about 20-40 amino acids in length.
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PMID:Rat liver polysome N alpha-acetyltransferase: substrate specificity. 184 56

A vaccinia virus (VV) vector was used to express rat plasma kallikrein (rPK) in the constitutively secreting cells, BSC-40, and in the endocrine regulated cells, AtT-20. Using a specific rPK antibody and a fluorogenic substrate, Phe-Phe-Arg-AMC, we demonstrated that in both cell lines VV infections resulted in the synthesis of an immunoreactive enzyme predominantly present as a zymogen which can be activated with trypsin. Stimulation of VV:rPK-infected AtT-20 cells with either 5mM 8-bromo-cAMP or 56 mM KCl resulted in a different pattern of rPK and ACTH secretion, strongly suggesting that rPK follows the constitutive secretory pathway. Finally, the 10% rPK activity found within AtT-20 cell extracts had no effect on pro-opiomelanocortin (POMC) processing either intracellularly or extracellularly. The above data show that the biosynthetic machinery of both cell lines analyzed does not allow the efficient activation of plasma prekallikrein. Finally, despite the PK's demonstrated ability to cleave various hormone precursors in vitro at pairs of basic residues, in vivo, we did not obtain evidence that this hepatic enzyme can also act as an intracellular pro-protein processing enzyme.
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PMID:Expression and sorting of rat plasma kallikrein in POMC-producing AtT-20 cells. 185 25

Previous animal and human studies have suggested an analgesic effect of phenylalanine involving endogenous opioid peptides. Phenylalanine was measured by a HPLC method with electrochemical detection and beta-endorphin by a specific radioimmunoassay in 14 lumbar cerebrospinal fluid samples from 13 patients with phenylketonuria. Cerebrospinal fluid beta-endorphin was also determined in 6 age-matched control subjects. We found a trend towards a higher beta-endorphin level in phenylketonuria (median 26.0 pM, range 13.0-37.8) than in the control subjects (20.6 pM, 12.7-28.0), P = 0.13. Cerebrospinal fluid concentrations of phenylalanine and beta-endorphin were significantly correlated (r = 0.68, P = 0.008). The results support the hypothesis that phenylalanine modifies the central endogenous opioid system.
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PMID:Correlation between cerebrospinal fluid phenylalanine and beta-endorphin in patients with phenylketonuria. 192 62

1. A sucrose-gap technique was used to investigate the neuromodulatory actions of enkephalins on non-adrenergic, non-cholinergic inhibitory junction potentials (IJPs) in the circular muscle of the human large intestine. 2. The native enkephalins, [Leu5]enkephalin (LENK) and [Met5]enkephalin (MENK) caused a concentration-dependent reduction in amplitude of IJPs without a significant effect on the smooth muscle membrane. 3. The actions of LENK and MENK were mimicked by the delta-selective opioid receptor agonists [D-Pen2, D-Pen5]enkephalin (DPDPE) and [D-Ala2, D-Leu5]enkephalin (DADLE). 4. The actions of LENK, MENK and DPDPE were antagonized to similar extents by the delta-selective opioid receptor antagonist ICI 174,864. 5. The mu-selective opioid receptor agonist [D-Ala2, Me Phe, Gly-ol5]enkephalin was approximately 100-fold less potent than any of the native or synthetic enkephalins at reducing the amplitude of the IJP. Dynorphin A and beta-endorphin both had very weak activity. 6. Responses to all of the agonists were inhibited by naloxone. The degree of antagonism of DPDPE or DADLE by naloxone (1 microM) was the same as that of LENK or MENK. 7. Neither MENK nor LENK affected hyperpolarization of the smooth muscle membrane induced by ATP or 5-hydroxytryptamine. Vasoactive intestinal polypeptide (1 pM-1 microM) did not produce any observable responses and this lack of reactivity was not affected by the enkephalins. 8. It is concluded that in the circular muscle of the human colon, LENK and MENK can act on prejunctional delta-opioid receptors to produce inhibition of non-adrenergic, non-cholinergic inhibitory neuromuscular transmission. Possible physiological significance of this prejunctional receptor is discussed.
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PMID:Enkephalins modulate inhibitory neuromuscular transmission in circular muscle of human colon via delta-opioid receptors. 196 52

The effects of intracerebroventricular (i.c.v.) administration of D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective mu-opioid receptor antagonist, (Allyl)2-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174864) and (N,N-Bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH (ICI 154129), selective delta-opioid receptor antagonists on blocking analgesia induced by beta-endorphin, morphine, D-Ala2-NMePhe4-Gly-ol-enkephalin (DAMGO), D-Ala2-D-Leu5-enkephalin (DADLE) and D-Pen2-enkephalin (DPDPE) administered i.c.v. were studied in male ICR mice. The analgesia was assessed by the tail-flick and paw-licking (hot-plate) tests. The potencies of opioid agonists injected i.c.v. for producing analgesia were DAMGO greater than DADLE greater than beta-endorphin greater than morphine greater than DPDPE. Intracerebroventricular administration of CTOP (0.05 micrograms) selectively antagonized inhibition of the tail-flick and paw-licking response induced by morphine, DAMGO or DADLE but not beta-endorphin or DPDPE. ICI 174864 (5 micrograms) and ICI 154129 (5 micrograms) injected i.c.v. selectively antagonized analgesia induced by DPDPE or DADLE but not beta-endorphin, morphine or DAMGO injected i.c.v. These results indicate that analgesia induced by morphine and DAMGO is mediated by the stimulation of mu-opioid receptors while analgesia induced by DPDPE is mediated by the stimulation of delta-opioid receptors. DADLE-induced analgesia is mediated by the stimulation of both mu- and delta-opioid receptors. Analgesia induced by beta-endorphin is mediated by neither mu- nor delta-opioid receptors.
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PMID:Different types of opioid receptors mediating analgesia induced by morphine, DAMGO, DPDPE, DADLE and beta-endorphin in mice. 197 34


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